Mouse embryos that lack either a maternal (androgenones) or paternal (gynogenones) genetic contribution fail to develop due to functional differences between the two genomes established through genetic imprinting during gametogenesis. It has been suggested that the genetic imprints are translated into differences in gene expression through modification of imprinted genes by factors in the egg. These """"""""modifier"""""""" factors are proposed to influence the methylation status or chromatin structure of imprinted genes. The nature and function of such modifiers have yet to be determined. Recent experiments indicate that androgenetic embryos offer a useful system for studying modifiers. The developmental capacity of androgenones varies with the maternal genotype (i.e. egg composition) due to strain-dependent modification of the male pronuclei. This modification is most likely mediated by one or more strain-specific modifiers which influence the expression of genes that are required for blastocoel formation. In this proposal,l will determine whether a single or multiple modifiers is/are responsible for this modification and, if a single modifier, determine its chromosomal location by recombinant inbred mapping. Immunofluorescence microscopy will be used to test the hypothesis that developmental failure in androgenones results from a defect in the establishment or differentiation of the putative trophectoderm lineage. These experiments will provide critical background information to be used in the future to pursue the identification and characterization of the genes encoding these modifiers and the genes that are regulated by them. This will further our understanding of imprinting, which contributes to specific disorders in man.
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